There are over 100,000 individuals in the United States whose kidney functions do not provide adequate urinary clearance of accumulated blood waste products. Approximately 90% of this population relies on hemodialysis (i.e., the so-called "artificial kidney") to remove impurities and fluids from their blood. Hemodialysis is also used in other instances, such as a direct or supportive measure during the treatment of certain heart conditions and scleroderma, and in the removal of metabolites from methyl alcohol poisoning.
The artificial kidney is a mechanical-chemical approach which utilizes both diffusion and ultrafiltration to remove impurities and fluids from blood. In dialysis, the blood of a patient is circulated from the patient's body into a dialyzer, where it flows over a semi-permeable membrane bathed in a cleansing or "dialysate" solution. Impurities in the blood pass through the membrane into the dialysate solution by diffusion. In addition, due to a difference in pressure between the blood and dialysate solution, excess fluid in the blood is removed by ultrafiltration. This process is known as "hemodialysis", and dialysis patients must generally undergo hemodialysis 2 to 3 times per week for 4-6 hours per treatment.
The first extracorporeal dialyzer was reported in 1960 and used a flat plate device containing blood with a dialysate solution flowing on the other side of a membrane. This was followed in the late 1960s by a twin-coil dialyzer and, soon thereafter, by the current hollow-fiber dialyzer. Hollow-fiber dialyzers are roughly shaped like a flashlight, and consist of 100 micron diameter membrane tubes (typically cellulosic or cellulosic ester based) through which the blood flows, and which are bundled together and immersed in a counter-current flow of dialysate solution. The dialyzer is, in turn, connected to a dialysis machine which contains a number of sensors (e.g., blood flow, blood leaks, blood pressure, etc.), as well as pumps, valves, flow pistons and flow diverters.
The portion of a representative dialysis machine which contains the dialyzer is represented in FIG. 1. More specifically, FIG. 1 illustrates the location of hollow-fiber dialyzer 1, blood flow from the patient 2, blood flow to the patient 3, dialysate solution flow into the dialyzer 4, dialysate solution flow out of the dialyzer 5 and pump 6 which controls blood flow through the dialyzer. Dialysate solution (about 500 ml/minute) is moved into and out of the dialyzer by a series of pumps, one of which extracts a specified amount of spent dialysis fluid from the circuit and replaces it with fresh dialysate. Impurities pass from the blood and into the dialysate by diffusion. In addition, because there is a difference in pressure between the blood and dialysate, excess fluid in the blood is removed by ultrafiltration. Within established safe limits, the trans-membrane pressure is allowed to change freely to any value that results from the dialyzer ultrafiltration rate chosen.
While the price of dialyzers has been significantly reduced since their initial introduction, the annual cost for patients who undergo hemodialysis 2 to 3 times per week with a so-called "single-use dialyzer" is quite high. Accordingly, much attention has been given to cleaning and sterilizing a dialyzer for repeated use by a given patient. In addition to the obvious amortization of equipment cost over the use-life of the dialyzer (i.e., typically greater than 10 reuses), patients experience fewer symptoms of "first-use-syndrome," which occurs when the patient's blood encounters the membrane and plastic components of a new dialyzer. With use, dialyzers become internally coated with the patient's own proteins (e.g., albumen, fibrinogen, globulin and immunological proteins) which minimizes the severity of such first-use reactions in subsequent dialysis sessions. Since reuse of dialyzers was first introduced in the mid-1960's, evidence has been accumulating that this practice is quite effective and, provided the dialyzer is adequately sterilized between uses, reuse has not been associated with any increase in the rate of infection resulting from dialysis.
To date, the most prevalent and least expensive hemodialyzer reprocessing sterilant has been formaldehyde, which is generally used in the form of a 4% aqueous solution. Formaldehyde is now used in 43% of the hemodialysis centers that reprocess dialyzers. However, those operating in the industry are becoming increasingly reluctant to use formaldehyde because of (a) the antibody formation which formaldehyde provokes, (b) the status of formaldehyde as a co-carcinogen and (c) formaldehyde's overall noxiousness in handling. Similar problems are associated with the related sterilant glutaraldehyde, used in 8% of reprocessing. A more recent sterilant is based on a peracetic acid/hydrogen peroxide combination, and accounts for 49% of reuse sterilant. This system, however, has been associated with an increased level of morbidity in patients exposed to dialyzers reprocessed using this sterilant.
A more effective and more compatible sterilant has been identified, and is based on the cidal species associated with chlorous acid. Such a sterilant was introduced into the hemodialyzer processing market by Alcide Corporation in 1985 under the trade name RenNew-D. The technology of this sterilant involved the combination of lactic acid with a metal chlorite to yield chlorous acid-containing disinfecting compositions. One such chlorous acid system was found to be more effective against bacteria (and bacterial spores) compared to a 4% aqueous formaldehyde solution, and was also able to destroy certain water-borne microorganisms (such as Mycobacteria chelonei) which had caused septic outbreaks and deaths in a number of clinics using formaldehyde for hemodialyzer reprocessing. Dialyzer reuse lifetimes were also significantly greater with the chlorous acid system, and the solutions were more "user friendly" than the formaldehyde-based and peracetic/peroxide-based sterilant systems. In addition, and in contrast to other dialyzer sterilants, the chlorous acid system did not denature the inner-protein coatings of dialyzer surfaces.
Practitioners did, however, experience certain problems with the chlorous acid sterilant RenNew-D. Specifically, random perforations appeared in several of the many blood-bearing cellulosic microtubules in dialyzers which had been treated with this product. These "holes" apparently resulted in several cases of septicemia in patients who had been reconnected to the disinfected dialyzers, where bacteria and/or bacterial fragments in the non-sterile dialysate solution passed through the membrane perforations into the patient's blood stream. This problem resulted in the product's subsequent removal from the market.
While significant advances have been made in the field of hemodialysis, particularly with regard to reprocessing dialyzers for multiple reuse by a single patient, significant disadvantages are encountered with existing sterilant solutions used for reprocessing. Accordingly, there is a need in the art for improved sterilant compositions suitable for use as reprocessing sterilants, as well as methods relating to their use. The present invention fulfills these needs, arid provides further related advantages.